About this Author

College chemistry, 1983

The 2002 Model

After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases.
To contact Derek email him directly: derekb.lowe@gmail.com
Twitter: Dereklowe

March 20, 2009

What Results Did You Have In Mind?

Posted by Derek

Of course, no sooner do I come out defending drug company research than we have this to think about:

"An influential Harvard child psychiatrist told the drug giant Johnson & Johnson that planned studies of its medicines in children would yield results benefiting the company, according to court documents dating over several years that the psychiatrist wants sealed. . .much of (Dr. Joseph Biederman's) work has been underwritten by drug makers for whom he privately consults. An inquiry by Senator Charles E. Grassley, Republican of Iowa, revealed last year that Dr. Biederman earned at least $1.6 million in consulting fees from drug makers from 2000 to 2007 but failed to report all but about $200,000 of this income to university officials.

. . .One set of slides in the documents referred to “Key Projects for 2004” and listed a planned trial to compare Risperdal, also known as risperidone, with competitors in managing pediatric bipolar disorder. The trial “will clarify the competitive advantages of risperidone vs. other neuroleptics,” the slide stated. All of the slides were prepared by Dr. Biederman, according to his sworn statement."

There are other examples. Some of this is marketing-speak, to be sure. But mixing up the marketing stuff with the inner workings of the clinical trials is a very bad idea. For sales and marketing people, it's always onward and upward, positive attitude, create-your-own-successful-reality. You most definitely do not want that worldview in a clinician: "Just the facts, ma'am" is more like it. And that doesn't sound like what we're seeing here.

Besides the non-reporting of revenue which is bad, I really don't interpret the statement that the trial "will clarify the competitive advantages of risperidone vs. other neuroleptics" as sinister.

If it would have said "will confirm" or "will cement" then yes, that's presupposing an outcome. "Will clarify" doesn't mean that at all to me. If previous studies had shown benefits A,B,and C over the competition and he proposed bigger or more conclusive studies which looked at benefits A,B,and C vs. the competition, then I really don't have a problem with that, as long as the studies are scientifically and ethically sound.

IMO, it's the "competitive advantages" phrase that sticks out. That should be something like "relative effectiveness". There's nothing at all wrong with comparing a new drug to old ones to see if it's better, but the statement as is carries an explicit assumption that there will be a "competitive advantage" for Risperdal, with the study just trying to measure how amazing the new drug is.

Partially it's semantic... no scientist is ever truly neutral, and often times we want a certain result. But we have to always acknowledge that our favorite hypothesis could be complete bunk, and be ready to throw it out if the experiments don't support it.

Derek, of course you will find examples of non corrupt industry-sponsored research. The question is whether the opportunities for corruption are disproportionally higher in that kind of research. The answer seems to be yes. It is easy to trivialize the allegations as isolated or anecdotal, but they are not isolated, and they are not anecdotal. There's something systemically wrong and we need to find a better way.

Palo there are literally thousands pharma sponsored studies involving thousands of researchers/sites. Please see http://clinicaltrials.gov/ct2/search/browse?brwse=spns_cat_INDUSTRY. This is active Clinical trials (in US only?) and there is plenty more industry sponsored work being done. So the few "bad events" seemed to be heavily out weighed by the numbers (that does not mean they are not serious or deplorable but to use to argue against all industry sponsorship is wrong).

The "well publicized" stories are isolated and anecdotal and I would argue because of redundant and external controls the answer is NO as to "whether the opportunities for corruption are disproportionally higher in that kind of research". Yes there are problems and systems can be improved but until you take the human elements out I am not sure can ever have absolute purity. Most "solutions" I have seen propose government and/or academic controls which probably will be worse (in time and cost for sure and doubtful less corruption). Usually government and university researchers barely know the rules much less are set up to abide by them (figures I have seen suggest univ sites have 2x more GCP violations than for-profit sites).

The bottom line is significant amounts of money have to come from somewhere to run these trials, and with money comes motive. Despite what some may think, the government is not without motive, and acedemics are certainly not without motive. Having been party to trials of both types (admittedly limited) I can tell you that the drive for positive results from acedemics is far and away more powerful than the drive from companies. The thing companies know is that the shit is going to hit the fan some day, and in a company you don't want to be near the blades when they start spinning. On the other hand, tenure provides a nice sheet of plastic for others.

And from today's Boston Globe we have Biederman promising J&J to develop new uses for their drugs, and that a future study "will support the effectiveness and safety of risperidone" in preschoolers.

Dr. Biederman is the most highly cited researcher in child psychiatry, according to ISI and his "research" appears to be marketing. It's a little preposterous to argue that this incident is "isolated and anecdotal." Companies give their money to people and institutions that will give them something back in return.

Who do you expect to pay 100's of millions of dollars for clinical trials? If I am a company with a promising new drug I am certainly not going to wait for the government to fork over the cash for the study. Pointing out cases of abuse is fine, they are certainly out there, and should be exposed and prosecuted. I just don't see an alternative system which is better.

Well there is need for transparency and clear rules in these relationships - otherwise nothing stops companies from being super nice to doctors running their clinical trials. With this much money at stake I would be more surprised if there was no corruption

In most companies there are really two types of groups (at least) running trials. One is called some variant of "Clinical Research" and is primarily responsible for pre-approval trials both prior to any approval and for approval of new label claims. The second type is "Medical Affairs" and they tend to run trials intended to get MDs to start using the drug and/or get citable publications where a label claim would be unlikely. Clinical folks tend to cop a bit of an attitude when referring to MA.

Clinical budgets usually come out of R&D whereas Med Affairs is covered by Sales and Marketing. Sounds to me like the Biederman work came out of the latter. It would be much easier to commit fraud in MA because the review is not as thorough. The data are likely to go to regulators only as part of an integrated summary and oftentimes only the safety portion is sent because the efficacy is off-label anyway. Journal review is not likely to catch fraud in a clinical trial.

It might surprise some that the worst influence of the business types on clinical research is not the pressure to produce positive results or spin results positively. The worst is that they will not let us shut down problematic sites because the MD is too influential. In every major trial with 40 sites one of the worst sites comes from the 35 or so regular MDs and the other worst site comes from the 5 or so key opinion leaders. Usually whatever fraud is involved is of the petty variety more like sloppiness than deception and the rest is lack of attention because they have a piece of every trial in the field. But I've seen worse and been battled every step of the way by folks saying this guy is too important to piss off.